The roles of continuous and discontinuous proliferations on hepatitis B virus infection.

The proliferation of both uninfected and infected hepatocytes, as well as the recycling effects of rcDNA-containing capsids are two key mechanisms playing significant roles in the persistence and clearance of hepatitis B virus (HBV) infection. In this study, the temporal dynamics of this viral infection is investigated through two intercellular mathematical models considering proliferation of both types of hepatocytes (uninfected and infected) and recycling effects of capsids. Both models are formulated on the basis of a key finding in the existing literature: mitosis of an infected hepatocytes yields in two uninfected progenies. In the first model (defined by P-model), we examine the continuous proliferation (which occur continuously), while the second one (defined by M-model) deals with the discontinuous proliferation (happen when the concentration of liver cells decreases to less than 70% of its initial concentration). The proposed models are calibrated with the experimental data obtained from an adult chimpanzee. Results of this study suggest that when both hepatocytes proliferate with equal rate, proliferation helps the individual in a rapid recovery from the acute infection whereas in case of chronic infection, the severity of the infection increases. On the other hand, if the infected hepatocytes proliferate at a different rate that of uninfected hepatocytes, the proliferation of uninfected hepatocytes contributes to increase the infection, but the proliferation of infected hepatocytes acts to reduce the infection from the long-term perspective. The global sensitivity analysis also shows the same results. Furthermore, it is also observed that the differences between the outcomes of continuous and discontinuous proliferations are significant and noteworthy.